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Chebib FT, Hanna C, Harris PC, Torres VE, Dahl NK. Autosomal Dominant Polycystic Kidney Disease: A Review. JAMA 2025; 333:1708-1719. [PMID: 40126492 DOI: 10.1001/jama.2025.0310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
Importance Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and is the most common inherited kidney disorder worldwide. ADPKD accounts for 5% to 10% of kidney failure in the US and Europe, and its prevalence in the US is 9.3 per 10 000 individuals. Observations ADPKD is typically diagnosed in individuals aged 27 to 42 years and is primarily caused by pathogenic variants in the PKD1 (78%) or PKD2 (15%) genes. Most persons with ADPKD have an affected parent, but de novo disease is suggested in 10% to 25% of families. More than 90% of patients older than 35 years have hepatic cysts, which may cause abdominal discomfort and occasionally require medical or surgical intervention. Hypertension affects 70% to 80% of patients with ADPKD, and approximately 9% to 14% develop intracranial aneurysms, which have a rupture rate of 0.57 per 1000 patient-years. Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age. The severity of kidney disease can be quantified using the Mayo Imaging Classification (MIC), which stratifies patients based on total kidney volume adjusted for height and age and ranges from 1A to 1E. Patients with MIC 1C to MIC 1E have larger kidneys because of more rapid growth (6%-10% per year) compared with those with MIC 1A and 1B (1%-5% per year) and have earlier progression to kidney replacement therapy, which occurs at a mean age of 58.4 years for MIC 1C, 52.5 years for MIC 1D, and 43.4 years for MIC 1E. Optimal management of ADPKD includes systolic blood pressure lower than 120 mm Hg for most patients, but lower than 110/75 mm Hg for patients with MIC 1C to 1E who have an estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m2 and are younger than 50 years, dietary sodium restriction (<2000 mg/d), weight management, and adequate hydration (>2.5 L daily). The vasopressin type 2 receptor antagonist tolvaptan reduces the annual rate of eGFR decline by 0.98 to 1.27 mL/min/1.73 m2 and is indicated for patients with MIC 1C to 1E or an eGFR decline greater than 3 mL/min/1.73 m2 per year to slow disease progression and delay the onset of kidney failure. Conclusion ADPKD is the most common genetic kidney disease worldwide and is characterized by progressive development of kidney cysts. Patients typically have hypertension and liver cysts, and 9% to 14% develop intracranial aneurysms. First-line treatment includes blood pressure control, dietary and weight management, and adequate hydration. Tolvaptan reduces the rate of eGFR decline for those at high risk of rapid progression to kidney failure.
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Affiliation(s)
- Fouad T Chebib
- Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida
| | - Christian Hanna
- Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
| | - Peter C Harris
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
| | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
| | - Neera K Dahl
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota
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Geertsema P, Gansevoort RT, Arici M, Capasso G, Cornec-Le Gall E, Furlano M, Fuster DG, Galletti F, Gómez Dos Santos V, Perez Gomez MV, Goumenos D, Halbritter J, Jambon E, Korst U, Leliveld-Kors AM, Musquera M, Figueiredo A, Nijenhuis T, Olsburgh J, Pol RA, Sayer JA, Stippel D, Torra R, Müller RU, Casteleijn NF. Nephrectomy in autosomal dominant polycystic kidney disease: a consensus statement of the ERA Genes & Kidney Working Group. Nephrol Dial Transplant 2025; 40:1032-1054. [PMID: 39848914 DOI: 10.1093/ndt/gfaf019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Indexed: 01/25/2025] Open
Abstract
A substantial number of patients with autosomal dominant polycystic kidney disease (ADPKD) undergo a nephrectomy, especially in workup for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians about which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD. A literature review was performed and extended to a meta-analysis when possible. For this purpose, PubMed and EMBASE were searched up to May 2024. Fifty-four publications, describing a total of 2391 procedures, were included. In addition, an exploratory questionnaire was sent to urologists, nephrologists, and transplant surgeons. These sources were used to develop practice points about indications, complications, mortality, and timing and technique of nephrectomy. In addition, data on renal embolization as a potential alternative to nephrectomy were explored and summarized. To reach consensus, practice points were defined and improved in three Delphi survey rounds by experts of the European Renal Association Working Group Genes & Kidney and the European Association of Urology Section of Transplantation Urology. A total of 23 practice points/statements were developed, all of which reached consensus. Among others, it was deemed that nephrectomy can be performed successfully for various indications and is an intermediate risk procedure with acceptable mortality and minimal impact on kidney graft function when performed before, in the same session or after transplantation. The complication rate seems to increase when the procedure is performed as an emergency. During the workup for transplantation, patient complaints should be assessed routinely by questionnaires to indicate symptom burden. Deciding on the need for nephrectomy and exploring potential alternatives such as kidney embolization should be a process of shared decision-making, preferably after multidisciplinary consultation.
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Affiliation(s)
- Paul Geertsema
- D epartment of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ron T Gansevoort
- D epartment of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Mustafa Arici
- Department of Nephrology, Faculty of Medicine, Hacettepe University, Altındağ, Ankara, Turkey
| | - Giovambattista Capasso
- Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
- Biogem Institute of Molecular Biology and Genetics, Ariano Irpino, Italy
| | - Emilie Cornec-Le Gall
- University of Brest, Inserm, Unité Mixte de Recherche 1078, Génétique, Génomique fonctionnelle et Biotechnologies, Centre Hospitalier Universitaire Brest, Centre de Références Maladies Rénales Héréditaires de l'Adulte et de l'Enfant MARHEA, Brest, France
| | - Monica Furlano
- Nephrology Department, Fundació Puigvert; Institut de Recerca Sant Pau (IR Sant Pau); Departament de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Daniel G Fuster
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | - Victoria Gómez Dos Santos
- Department of Urology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá, Madrid, Spain
| | | | - Dimitrios Goumenos
- Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece
| | - Jan Halbritter
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Eva Jambon
- Department of Diagnostic and Interventional Radiology, Pellegrin University Hospital, Bordeaux, France
| | - Uwe Korst
- PKD International, Geneva, Switzerland
| | - Anna M Leliveld-Kors
- Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Mireia Musquera
- Department of Urology, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Arnaldo Figueiredo
- Department of Urology and Renal Transplantation, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Tom Nijenhuis
- Department of Nephrology, Research Institute of Medical Innovations, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Jonathon Olsburgh
- Department of Urology & Transplant Surgery, Guy's & St Thomas' NHS Foundation Trust, London, UK
| | - Robert A Pol
- Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - John A Sayer
- Bioscience Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Renal Services, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Dirk Stippel
- Department of General, Visceral, Cancer and Transplant Surgery, University Hospital Cologne, Köln, Germany
| | - Roser Torra
- Nephrology Department, Fundació Puigvert; Institut de Recerca Sant Pau (IR Sant Pau); Departament de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Roman-Ulrich Müller
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
| | - Niek F Casteleijn
- Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Urology, Ommelander Ziekenhuis Groningen, Scheemda, The Netherlands
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Yan Z, Wang Y, Zeng W, Hui J, Yang B, Xu J, Miao Y, Xia R. Antibiotic-driven pathogen replacement events in a kidney transplant recipient with ADPKD: a case report. BMC Infect Dis 2025; 25:423. [PMID: 40140753 PMCID: PMC11948758 DOI: 10.1186/s12879-025-10804-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 03/14/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Retaining the native bilateral kidneys after transplantation is a common treatment for patients with end-stage autosomal dominant polycystic kidney disease. However, this strategy poses the risks of potential complications from polycystic kidney infection. The efficiency of antibiotic therapy and the optimal time for native nephrectomy in managing these infections remain uncertain. CASE PRESENTATION We report a case of a kidney transplant recipient with retained bilateral polycystic kidneys who experienced recurrent cyst and bloodstream infections, accompanied by antibiotic-driven pathogen replacement. After multiple failed attempts at antibiotic therapy, the patient subsequently underwent unilateral polycystic kidney resection. Subsequently, a new infection episode occurred, leading to the other native nephrectomy. Cystic tissue and fluid samples were collected from both shallow and deep layers of the polycystic kidneys, along with peripheral blood and urine samples. These samples were analyzed using microbial culture, metagenome sequencing, and digital polymerase chain reaction to identify infectious pathogens. Pathogen replacement occurred across different infection episodes, with the dominant bacterial species being Escherichia coli, Klebsiella aerogenes, and Enterococcus faecium, in succession. CONCLUSIONS This case highlights the replacement of dominant pathogens under antibiotic selection pressure in polycystic kidney infections, primarily involving gram-negative bacilli. When initial and subsequent antibiotic therapy fail, re-evaluation of the cyst infection definition is necessary, and preemptive native nephrectomy should be considered.
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Affiliation(s)
- Ziyan Yan
- Department of Transplantation, Nanfang Hospital, Southern Medical Univerisity, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Yuchen Wang
- Department of Transplantation, Nanfang Hospital, Southern Medical Univerisity, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Wenli Zeng
- Department of Transplantation, Nanfang Hospital, Southern Medical Univerisity, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Jialiang Hui
- Department of Transplantation, Nanfang Hospital, Southern Medical Univerisity, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Bin Yang
- Center for Infectious Diseases Vision Medicals Co., Ltd., Guangzhou, China
| | - Jian Xu
- Department of Transplantation, Nanfang Hospital, Southern Medical Univerisity, 1838 North Guangzhou Avenue, Guangzhou, 510515, China
| | - Yun Miao
- Department of Transplantation, Nanfang Hospital, Southern Medical Univerisity, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
| | - Renfei Xia
- Department of Transplantation, Nanfang Hospital, Southern Medical Univerisity, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
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Waiser J, Klotsche J, Glander P, Schmidt D, Naik M, Liefeldt L, Budde K, Halbritter J, Halleck F, Zukunft B, Peters R, Friedersdorff F, Lachmann N, Eckardt KU, d'Anjou L, Bachmann F. Kidney transplantation in patients with polycystic kidney disease: increased risk of infection does not compromise graft and patient survival. Clin Kidney J 2024; 17:sfae330. [PMID: 39664987 PMCID: PMC11630747 DOI: 10.1093/ckj/sfae330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Indexed: 12/13/2024] Open
Abstract
Background Patients with autosomal dominant polycystic kidney disease (ADPKD) represent >10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear. Methods Between 2000 and 2017 we performed 193 kidney transplantations in patients with ADPKD. In 189 patients, we assessed the occurrence, frequency, and severity of infection episodes requiring inpatient treatment and their impact on graft and patient outcomes compared with 189 matched controls. Risk factors were analyzed by uni- and multivariable analyses. Results During a mean observation period of 77 months UTIs occurred more frequently in ADPKD patients (39.1% vs. 26.7%, P = .022; 0.8 ± 1.4 vs. 0.5 ± 1.1 episodes, P < .001). Eight ADPKD patients suffered from 19 episodes of liver cyst infection. Steroid medication (RR 3.04; P < .001) and recipient age (RR 1.05; P = .003) increased the risk for UTI/urosepsis, while nephrectomy reduced it (unilateral, RR 0.60; P = .088; bilateral, RR 0.45; P = .020). Patient survival was similar in both groups. The risk of graft failure was lower in ADPKD patients [hazard ratio (HR) 0.67; P = .047] due to a lower risk of death-censored graft loss (HR 0.47; P = .014). Donor age (HR 1.34; P = .002) and rejection (HR 8.47; P < .001) were risk factors for death-censored graft loss. Conclusions ADPKD patients are at increased risk of UTI and liver cyst infection after transplantation. Steroid medication and recipient age seem to increase the risk of UTI/urosepsis, while nephrectomy seems to reduce it. Nevertheless, patient survival was similar compared to non-ADPKD patients and death-censored graft survival even better.
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Affiliation(s)
- Johannes Waiser
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Jens Klotsche
- German Rheumatism Research Center Berlin – a Leibniz Institute, Berlin, Germany
| | - Petra Glander
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Danilo Schmidt
- Business Unit IT, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Marcel Naik
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Lutz Liefeldt
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Jan Halbritter
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Bianca Zukunft
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Robert Peters
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Frank Friedersdorff
- Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Nils Lachmann
- Institute of Transfusion Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Kai-Uwe Eckardt
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Leonie d'Anjou
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Friederike Bachmann
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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Treglia G, Albano D, Rizzo A, Bellasi A, Glaudemans AWJM, Gheysens O. Performance of [ 18F]FDG PET/CT in Diagnosing Cyst Infections in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and a Bivariate Meta-Analysis. Diagnostics (Basel) 2024; 14:1603. [PMID: 39125479 PMCID: PMC11312050 DOI: 10.3390/diagnostics14151603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has been suggested as a useful imaging method for diagnosing cyst infections in patients with autosomal dominant polycystic kidney disease (ADPKD). The aim of this article is to provide evidence-based data in this setting. METHODS A systematic literature review (exploring several bibliographic databases) and a bivariate meta-analysis were carried out to calculate the pooled diagnostic performance of [18F]FDG PET/CT in diagnosing probable cyst infection in ADPKD. RESULTS Ten studies (282 PET/CT scans and 249 patients) were included in the analysis. The pooled sensitivity and specificity of [18F]FDG PET/CT in this setting were 84.6% (95% confidence interval: 75.4-90.7) and 94.9% (95% confidence interval: 72.6-99.2), respectively, without statistical heterogeneity or significant publication bias. [18F]FDG PET/CT significantly changed patient management in more than half of ADPKD patients with suspected cyst infection. CONCLUSIONS [18F]FDG PET/CT has high performance in diagnosing probable cyst infections in ADPKD patients with an impact on management in the majority of patients. Although more studies are warranted, the provided evidence-based data are an important step towards the integration of [18F]FDG PET/CT in clinical and diagnostic guidelines on probable cyst infection in ADPKD patients.
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Affiliation(s)
- Giorgio Treglia
- Division of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland;
- Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland
| | - Domenico Albano
- Division of Nuclear Medicine, ASST Spedali Civili Brescia, 25123 Brescia, Italy;
- Nuclear Medicine Department, University of Brescia, 25121 Brescia, Italy
| | - Alessio Rizzo
- Division of Nuclear Medicine, Candiolo Cancer Institute, FPO-IRCCS, 10060 Turin, Italy;
| | - Antonio Bellasi
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland;
- Service of Nephrology, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland
| | - Andor W. J. M. Glaudemans
- Medical Imaging Center, Department of Nuclear Medicine & Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700-RB Groningen, The Netherlands;
| | - Olivier Gheysens
- Department of Nuclear Medicine, Cliniques Universitaires Saint-Luc and Institute of Clinical and Experimental Research (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium;
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Rothem Y, Askenasy E, Siman-Tov M, Davidov Y, Hoffman T, Mor E, Hod T. Elevated hemoglobin levels in renal transplant recipients with polycystic kidney disease versus other etiologies: exploring mechanisms and implications for outcomes. J Nephrol 2024; 37:1523-1537. [PMID: 38427307 PMCID: PMC11473538 DOI: 10.1007/s40620-023-01868-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 12/14/2023] [Indexed: 03/02/2024]
Abstract
BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD)-related end-stage kidney disease (ESKD) often necessitates transplantation. However, the impact of ADPKD on post-transplant outcomes, specifically hemoglobin levels, remains unknown. METHODS We retrospectively analyzed 513 Kidney Transplant Recipients (KTRs), of whom 81 had ESKD due to ADPKD (20 with pre-transplant native nephrectomy and 61 without). Hemoglobin levels were evaluated at multiple time intervals post-transplant. RESULTS Kidney transplant recipients with ADPKD vs. KTRs with ESKD due to other causes exhibited significantly higher hemoglobin levels in repeated measurement analysis. Multivariable analyses confirmed ADPKD as an independent predictor for elevated hemoglobin levels. In a multivariable logistic regression analysis, the odds for maximum hemoglobin > 15 mg/dL at 3-12 months post-transplant were more than twice as high in ADPKD patients vs. all the other KTRs (Odds Ratio [OR] 2.31, 95% Confidence Interval [CI] 1.3-4.13, p < 0.001). Pre-transplant native nephrectomy revealed a trend toward lower hemoglobin levels. Elevated hemoglobin levels were linked to improved estimated glomerular filtration rate (eGFR) at one year post-transplant. Patient survival was enhanced among KTRs with ADPKD compared to other ESKD causes. CONCLUSIONS Kidney transplant recipients with ADPKD exhibited elevated hemoglobin levels post-transplant, possibly due to prolonged native kidney erythropoietin production. These elevated hemoglobin levels were linked to improved outcomes, including allograft function and patient survival. Future research should further investigate the underlying mechanisms driving favorable ADPKD KTR outcomes.
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Affiliation(s)
- Yael Rothem
- Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Enosh Askenasy
- Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
- Renal Transplant Center, Sheba Medical Center, Tel Hashomer, Israel
| | - Maya Siman-Tov
- Department of Emergency and Disaster Management, School of Public Health, Tel-Aviv University, Tel Aviv, Israel
| | - Yana Davidov
- Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
- Liver Disease Center, Sheba Medical Center, Tel Hashomer, Israel
| | - Tomer Hoffman
- Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
- Infectious Diseases Unit, Sheba Medical Center, Tel Hashomer, Israel
| | - Eytan Mor
- Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
- Renal Transplant Center, Sheba Medical Center, Tel Hashomer, Israel
| | - Tammy Hod
- Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
- Renal Transplant Center, Sheba Medical Center, Tel Hashomer, Israel.
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Hogan MC, Simmons K, Ullman L, Gondal M, Dahl NK. Beyond Loss of Kidney Function: Patient Care in Autosomal Dominant Polycystic Kidney Disease. KIDNEY360 2023; 4:1806-1815. [PMID: 38010035 PMCID: PMC10758524 DOI: 10.34067/kid.0000000000000296] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 10/26/2023] [Indexed: 11/29/2023]
Abstract
Patients with autosomal dominant polycystic kidney disease benefit from specialized care over their lifetimes, starting with diagnosis of the condition with ongoing discussion of both the renal course and extra-renal issues. Both renal and extra-renal issues may continue to cause major morbidity even after successful kidney transplant or initiation of RRT, and extra-renal disease aspects should always be considered as part of routine management. In this review, we will focus on updates in pain/depression screening, cardiac manifestations, liver and pancreatic cysts, kidney stone management, and genetic counseling. In some instances, we have shared our current clinical practice rather than an evidence-based guideline. We anticipate more standardization of care after the release of the Kidney Disease Improving Global Outcomes guidelines for management in autosomal dominant polycystic kidney disease later this year.
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Affiliation(s)
- Marie C. Hogan
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Kathryn Simmons
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Lawrence Ullman
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Maryam Gondal
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Neera K. Dahl
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
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Zhuang J, Aierken A, Yalikun D, Zhang J, Wang X, Ren Y, Tian X, Jiang H. Case report: Genotype-phenotype characteristics of nine novel PKD1 mutations in eight Chinese patients with autosomal dominant polycystic kidney disease. Front Med (Lausanne) 2023; 10:1268307. [PMID: 37901409 PMCID: PMC10600478 DOI: 10.3389/fmed.2023.1268307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 09/18/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder. The PKD1 gene is responsible for the majority of ADPKD cases, and the mutations in this gene exhibit high genetic diversity. This study aimed to investigate the association between genotype and phenotype in ADPKD patients with PKD1 gene mutations through pedigree analysis. Methods Eight Chinese pedigrees affected by ADPKD were analyzed using whole-exome sequencing (WES) on peripheral blood DNA. The identified variants were validated using Sanger sequencing, and clinical data from the patients and their families were collected and analyzed. Results Nine novel mutation sites in PKD1 were discovered across the pedigrees, including c.4247T > G, c.3298_3301delGAGT, c.4798A > G, c.7567G > A, c.11717G > C, c.7703 + 5G > C, c.3296G > A, c.8515_8516insG, and c.5524C > A. These mutations were found to be associated with a range of clinical phenotypes, including chronic kidney disease, hypertension, and polycystic liver. The age of onset and disease progression displayed significant heterogeneity among the pedigrees, with some individuals exhibiting early onset and rapid disease progression, while others remained asymptomatic or had milder disease symptoms. Inheritance patterns supported autosomal dominant inheritance, as affected individuals inherited the mutations from affected parents. However, there were instances of individuals carrying the mutations who remained asymptomatic or exhibited milder disease phenotypes. Conclusion This study highlights the importance of comprehensive genotype analysis in understanding the progression and prognosis of ADPKD. The identification of novel mutation sites expands our knowledge of PKD1 gene mutations. These findings contribute to a better understanding of the disease and may have implications for personalized therapeutic strategies.
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Affiliation(s)
- Jing Zhuang
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
| | - Ailima Aierken
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
| | - Dilina Yalikun
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
| | - Jun Zhang
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
| | - Xiaoqin Wang
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
| | - Yongfang Ren
- Department of Radiology and Medical Imaging, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
| | - Xuefei Tian
- Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States
| | - Hong Jiang
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China
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9
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Bugazia S, Hogan MC. Extrarenal Manifestations: Polycystic Liver Disease and Its Complications. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:440-453. [PMID: 37943238 DOI: 10.1053/j.akdh.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
The liver is the commonest site of involvement outside of the kidney in autosomal dominant polycystic kidney disease. Most individuals with polycystic liver disease are asymptomatic and require no therapeutic interventions, but a small number of affected individuals who experience symptomatic polycystic liver disease develop medical complications as a result of massive enlargement of cyst number and size and hepatic parenchyma and its subsequent associated complications. This can lead to deterioration in overall health and quality of life, increasing morbidity and mortality. In this review, we will touch upon disease pathogenesis, prevalence, and complications and discuss recent advances in surgical and medical management.
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Affiliation(s)
- Seif Bugazia
- Division of Nephrology & Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Marie C Hogan
- Division of Nephrology & Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
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10
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Casteleijn NF, Geertsema P, Koorevaar IW, Inkelaar FD, Jansen MR, Lohuis SJ, Meijer E, Pol RA, Sanders JS, van de Streek PE, Leliveld AM, Gansevoort RT. The Need for Routine Native Nephrectomy in the Workup for Kidney Transplantation in Autosomal Dominant Polycystic Kidney Disease Patients. Urol Int 2023; 107:148-156. [PMID: 35810740 PMCID: PMC9945191 DOI: 10.1159/000525575] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/14/2022] [Indexed: 11/19/2022]
Abstract
INTRODUCTION There is no consensus if nor when a native nephrectomy should be performed in the workup for kidney transplantation in ADPKD patients. In our PKD Expertise Center, a restrictive approach is pursued in which nephrectomy is performed only in patients with severe complaints, i.e., in case of serious volume-related complaints, lack of space for the allograft, recurrent cyst infections, persistent cyst bleedings, or chronic refractory pain. We analyzed in a retrospective cohort study whether this approach is justified. METHODS All ADPKD patients who received kidney transplantation between January 2000 and January 2019 were reviewed. Patients were subdivided into three groups: no nephrectomy (no-Nx), nephrectomy performed before (pre-Tx), or after kidney transplantation (post-Tx). Simultaneous nephrectomy together with transplantation were not performed in our center. RESULTS 391 patients (54 ± 9 years, 55% male) were included. The majority of patients did not undergo a nephrectomy (n = 257, 65.7%). A nephrectomy was performed pre-Tx in 114 patients (29.2%). After Tx, nephrectomy was performed in only 30 patients (7.7%, median 4.4 years post-Tx). Surgery-related complication rates did not differ between both groups (38.3% pre-Tx vs. 27.0% post-Tx, p = 0.2), nor were there any differences in 10-year patient survival (74.4% pre-Tx vs. 80.7% post-Tx vs. 67.6% no-Nx, p = 0.4), as well as in 10-year death-censored graft survival (84.4% pre-Tx vs. 85.5% post-Tx vs. 90.0% no-Nx, p = 0.9). CONCLUSIONS This study indicates that with a restrictive nephrectomy policy in the workup for kidney transplantation, only a part of ADPKD patients need a native nephrectomy.
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Affiliation(s)
- Niek F. Casteleijn
- Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands,*Niek F. Casteleijn,
| | - Paul Geertsema
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Iris W. Koorevaar
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Friso D.J. Inkelaar
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Marnix R. Jansen
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Steven J. Lohuis
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Esther Meijer
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Robert A. Pol
- Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Jan-Stephan Sanders
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Peter E. van de Streek
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Anna M. Leliveld
- Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ron T. Gansevoort
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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11
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Simonov PA, Firsov MA, Arutunyan VS, Laletin DI, Alekseeva EA. Options for approaches to nephrectomy in patients with end-stage chronic kidney disease caused by autosomal dominant polycystic kidney disease: A review. CONSILIUM MEDICUM 2022. [DOI: 10.26442/20751753.2022.10.201829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Autosomal-dominant polycystic kidney disease is a common kidney disease that affects all racial groups around the world, occupies one of the leading places in the structure of urological diseases and forms a significant contribution to the structure of all causes leading to the end stage of chronic renal failure, disabling patients in this group and hence leading to the inevitability of renal replacement therapy. A highly effective clinical method for replacing lost kidney function is kidney transplantation. Based on the fact that the number of patients with this pathology is increasing, it is necessary to search for and introduce clear criteria for the best care, taking into account the high likelihood of developing infectious complications, hematuria, the absence or presence of diuresis, arterial hypertension in this category of patients. The article reflects the various methods of nephrectomy in patients suffering from autosomal dominant polycystic kidney disease, as well as how approaches to nephrectomy have evolved. The results of complications, as well as patient and graft survival in domestic and foreign studies, in which bilateral or ipsilateral nephrectomy was used using open or laparoscopic access before, during or after kidney transplantation, are demonstrated. Preference is rightfully given to minimally invasive methods of surgical treatment. Taking into account the already reduced resources of the organism of these patients, the volume and method of surgical treatment should be carefully chosen, taking into account safety, efficacy and risk minimization.
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12
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Luan J, Kopp JB, Zhou H. N6-methyladenine RNA Methylation Epigenetic Modification and Kidney Diseases. Kidney Int Rep 2022; 8:36-50. [PMID: 36644366 PMCID: PMC9831943 DOI: 10.1016/j.ekir.2022.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 10/01/2022] [Accepted: 10/10/2022] [Indexed: 11/06/2022] Open
Abstract
RNA methylation modification is a rapidly developing field in epigenetics. N6-methyladensine (m6A) is the most common internal modification in eukaryotic mRNA. m6A group regulates RNA splicing, stability, translocation, and translation. Enzymes catalyzing this process were termed as writers, erasers, and readers. Recent studies have focused on exploring the role of RNA methylation in human diseases. RNA methylation modifications, particularly m6A, play important roles in the pathogenesis of kidney diseases. In this review, we provide a brief description of m6A and summarize the impact of m6A on acute and chronic kidney disease (CKD) and possible future study directions for this research.
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Affiliation(s)
- Junjun Luan
- Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jeffrey B. Kopp
- Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, Bethesda, Maryland, USA,Jeffrey B. Kopp, Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, 10 Center Drive, 3N116, Bethesda, Maryland 20892-1268, USA.
| | - Hua Zhou
- Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China,Correspondence: Hua Zhou, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Shenyang, Liaoning 110004, China.
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13
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McGill RL, Saunders MR, Hayward AL, Chapman AB. Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in the United States. Clin J Am Soc Nephrol 2022; 17:976-985. [PMID: 35725555 PMCID: PMC9269641 DOI: 10.2215/cjn.00840122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 04/14/2022] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND OBJECTIVES Autosomal dominant polycystic kidney disease (ADPKD) occurs at conception and is often diagnosed decades prior to kidney failure. Nephrology care and transplantation access should be independent of race and ethnicity. However, institutional racism and barriers to health care may affect patient outcomes in ADPKD. We sought to ascertain the effect of health disparities on outcomes in ADPKD by examining age at onset of kidney failure and access to preemptive transplantation and transplantation after dialysis initiation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Retrospective cohort analyses of adults with ADPKD in the United States Renal Data System from January 2000 to June 2018 were merged to US Census income data and evaluated by self-reported race and ethnicity. Age at kidney failure was analyzed in a linear model, and transplant rates before and after dialysis initiation were analyzed in logistic and proportional hazards models in Black and Hispanic patients with ADPKD compared with White patients with ADPKD. RESULTS A total of 41,485 patients with ADPKD were followed for a median of 25 (interquartile range, 5-54) months. Mean age was 56±12 years; 46% were women, 13% were Black, and 10% were Hispanic. Mean ages at kidney failure were 55±13, 53±12, and 57±12 years for Black patients, Hispanic patients, and White patients, respectively. Odds ratios for preemptive transplant were 0.33 (95% confidence interval, 0.29 to 0.38) for Black patients and 0.50 (95% confidence interval, 0.44 to 0.56) for Hispanic patients compared with White patients. Transplant after dialysis initiation was 0.61 (95% confidence interval, 0.58 to 0.64) for Black patients and 0.78 (95% confidence interval, 0.74 to 0.83) for Hispanic patients. CONCLUSIONS Black and Hispanic patients with ADPKD reach kidney failure earlier and are less likely to receive a kidney transplant preemptively and after initiating dialysis compared with White patients with ADPKD.
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Affiliation(s)
- Rita L. McGill
- Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Milda R. Saunders
- Section of General Medicine, Department of Medicine, University of Chicago, Chicago, Illinois
| | | | - Arlene B. Chapman
- Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois
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14
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Darius T, Bertoni S, De Meyer M, Buemi A, Devresse A, Kanaan N, Goffin E, Mourad M. Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival. World J Transplant 2022; 12:100-111. [PMID: 35663541 PMCID: PMC9136716 DOI: 10.5500/wjt.v12.i5.100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/11/2021] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The lack of space, as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms, remains controversial. AIM To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease. METHODS One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without (kidney transplant alone (KTA) group) and 77 with associated ipsilateral nephrectomy (KTIN group), were retrospectively reviewed. Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival. RESULTS Creation of space for future graft positioning was the main reason (n = 74, 96.1%) for associated ipsilateral nephrectomy. No significant difference in surgical comorbidity (lymphocele, wound infection, incisional hernia, wound hematoma, urinary infection, need for blood transfusion, hospitalization stay, Dindo Clavien classification and readmission rate) was observed between the two study groups. The incidence of primary nonfunction and delayed graft function was comparable in both groups [0% and 2.6% (P = 0.497) and 9.1% and 16.9% (P = 0.230), respectively, in the KTA and KTIN group]. The 1- and 5-year graft survival were 94.8% and 90.3%, and 100% and 93.8%, respectively, in the KTA and KTIN group (P = 0.774). The 1- and 5-year patient survival were 96.1% and 92.9%, and 100% and 100%, respectively, in the KTA and KTIN group (P = 0.168). CONCLUSION Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short- and long-term graft survival.
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Affiliation(s)
- Tom Darius
- Surgical and Abdominal Transplantation Unit, University Clinics Saint Luc, Brussels 1200, Belgium
| | - Sébastien Bertoni
- Surgical and Abdominal Transplantation Unit, University Clinics Saint Luc, Brussels 1200, Belgium
| | - Martine De Meyer
- Surgical and Abdominal Transplantation Unit, University Clinics Saint Luc, Brussels 1200, Belgium
| | - Antoine Buemi
- Surgical and Abdominal Transplantation Unit, University Clinics Saint Luc, Brussels 1200, Belgium
| | - Arnaud Devresse
- Division of Nephrology, University Clinics Saint Luc, Brussels 1200, Belgium
| | - Nada Kanaan
- Division of Nephrology, University Clinics Saint Luc, Brussels 1200, Belgium
| | - Eric Goffin
- Division of Nephrology, University Clinics Saint Luc, Brussels 1200, Belgium
| | - Michel Mourad
- Surgical and Abdominal Transplantation Unit, University Clinics Saint Luc, Brussels 1200, Belgium
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15
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Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that leads to chronic kidney disease and end-stage kidney disease (ESKD). Polycystic liver disease (PCLD) is the most common extrarenal manifestation of ADPKD. Though isolated PCLD and PCLD due to ADPKD are genetically distinct, they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function. Tolvaptan use in ADPKD can slow down the deterioration of renal function and growth of cysts. Somatostatin analogs can slow the growth of polycystic livers but the effect is short-lived. The only curative therapy for PCLD is liver transplantation. Renal transplantation can significantly improve survival in patients with ESKD due to ADPKD.
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Affiliation(s)
- Rebecca Roediger
- Division of Liver Disease, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA.
| | - Douglas Dieterich
- Division of Liver Disease, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA
| | - Pramodh Chanumolu
- Division of Nephrology, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA
| | - Priya Deshpande
- Division of Nephrology, Department of Medicine, Icahn School of Medicine, 1 Gustave L Levy Place, Box 1123, New York, NY 10029, USA
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16
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Chan JEZ, Kuah Z, Bhattacharjya S, Olakkengil SA. Recurrent thromboses and major vessel compressions in autosomal dominant polycystic kidney disease. J Surg Case Rep 2022; 2022:rjac012. [PMID: 35169439 PMCID: PMC8840890 DOI: 10.1093/jscr/rjac012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 01/04/2022] [Indexed: 12/24/2022] Open
Abstract
A 41-year-old man with autosomal dominant polycystic kidney disease (ADPKD), who had multiple previous unprovoked thrombotic events and without a known coagulopathic disorder, presented with symptomatic extensive thrombus distal to the compression site of the left common iliac vein by a dominant cyst in the left inferior renal pole. This was managed with inferior vena cava filter insertion, left nephrectomy and warfarinization. Later, there was inferior vena cava compression by the right polycystic kidney, leading to elective right nephrectomy. Post-renal transplantation, he had further episodes of partial dialysis access stenosis and extensive thromboses in the left deep and right superficial venous systems of the lower limbs despite absence of extrinsic compression. This represents the first report of recurrent mass effect and thromboembolic events in ADPKD, both before and after nephrectomy and anticoagulation. The potential increased thromboembolic risks among patients with ADPKD warrant further investigation.
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Affiliation(s)
- Joel Ern Zher Chan
- Central and Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
| | - Zhihong Kuah
- Central and Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia
| | - Shantanu Bhattacharjya
- Central and Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia
| | - Santosh Antony Olakkengil
- Central and Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
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17
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Ronsin C, Chaba A, Suchanek O, Coindre JP, Kerleau C, Garandeau C, Houzet A, Cantarovich D, Dantal J, Blancho G, Giral M, Couvrat-Desvergnes G, Ville S. Incidence, risk factors and outcomes of kidney and liver cyst infection in kidney transplant recipient with autosomal dominant polycystic kidney disease. Kidney Int Rep 2022; 7:867-875. [PMID: 35497795 PMCID: PMC9039903 DOI: 10.1016/j.ekir.2022.01.1062] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/12/2022] [Accepted: 01/24/2022] [Indexed: 12/11/2022] Open
Abstract
Introduction Methods Results Conclusion
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18
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Abstract
Genetic diseases cause numerous complex and intractable pathologies. DNA sequences encoding each human's complexity and many disease risks are contained in the mitochondrial genome, nuclear genome, and microbial metagenome. Diagnosis of these diseases has unified around applications of next-generation DNA sequencing. However, translating specific genetic diagnoses into targeted genetic therapies remains a central goal. To date, genetic therapies have fallen into three broad categories: bulk replacement of affected genetic compartments with a new exogenous genome, nontargeted addition of exogenous genetic material to compensate for genetic errors, and most recently, direct correction of causative genetic alterations using gene editing. Generalized methods of diagnosis, therapy, and reagent delivery into each genetic compartment will accelerate the next generations of curative genetic therapies. We discuss the structure and variability of the mitochondrial, nuclear, and microbial metagenomic compartments, as well as the historical development and current practice of genetic diagnostics and gene therapies targeting each compartment.
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Affiliation(s)
- Theodore L Roth
- Medical Scientist Training Program, University of California, San Francisco, California 94143, USA; .,Department of Microbiology and Immunology and Diabetes Center, University of California, San Francisco, California 94143, USA.,Innovative Genomics Institute, University of California, Berkeley, California 94720, USA.,Gladstone Institutes, San Francisco, California 94158, USA
| | - Alexander Marson
- Department of Microbiology and Immunology and Diabetes Center, University of California, San Francisco, California 94143, USA.,Innovative Genomics Institute, University of California, Berkeley, California 94720, USA.,Gladstone Institutes, San Francisco, California 94158, USA.,Department of Medicine, University of California, San Francisco, California 94143, USA.,Parker Institute for Cancer Immunotherapy, San Francisco, California 94129, USA.,Chan Zuckerberg Biohub, San Francisco, California 94158, USA.,Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94158, USA
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19
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Rosenberg S, Virmani S, Klarman S, Santovasi S, Dai F, Dahl NK. Mayo Imaging Classification May Be Useful in Determining the Need for Nephrectomy in ADPKD. KIDNEY360 2020; 2:325-330. [PMID: 35373011 PMCID: PMC8740992 DOI: 10.34067/kid.0003902020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 12/29/2020] [Indexed: 02/04/2023]
Affiliation(s)
- Stephanie Rosenberg
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Sarthak Virmani
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Sharon Klarman
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Samantha Santovasi
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
| | - Feng Dai
- Biostatistics, Yale University School of Public Health, New Haven, Connecticut
| | - Neera K. Dahl
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
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20
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Bhutani G, Astor BC, Mandelbrot DA, Mankowski-Gettle L, Ziemlewicz T, Wells SA, Frater-Rubsam L, Horner V, Boyer C, Laffin J, Djamali A. Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients with Polycystic Kidney Disease. KIDNEY360 2020; 2:312-324. [PMID: 35373032 PMCID: PMC8740986 DOI: 10.34067/kid.0001182019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 12/03/2020] [Indexed: 02/04/2023]
Abstract
Background Polycystic kidney disease (PKD) accounts for approximately 15% of kidney transplants, but long-term outcomes in patients with PKD who have received a kidney transplant are not well understood. Methods In primary recipients of kidney transplants at our center (1994-2014), we compared outcomes of underlying PKD (N=619) with other native diseases (non-PKD, N=4312). Potential factors influencing outcomes in PKD were evaluated using Cox proportional-hazards regression and a rigorous multivariable model. Results Patients with PKD were older and were less likely to be sensitized or to experience delayed graft function (DGF). Over a median follow-up of 5.6 years, 1256 of all recipients experienced death-censored graft failure (DCGF; 115 patients with PKD) and 1617 died (154 patients with PKD). After adjustment for demographic, dialysis, comorbid disease, surgical, and immunologic variables, patients with PKD had a lower risk of DCGF (adjusted hazard ratio [aHR], 0.73; 95% CI, 0.57 to 0.93; P=0.01) and death (aHR, 0.62; 95% CI, 0.51 to 0.75; P<0.001). In our multiadjusted model, calcineurin-inhibitor (CNI) use was associated with lower risk of DCGF (aHR, 0.45; 95% CI, 0.26 to 0.76; P=0.003), whereas HLA mismatch of five to six antigens (aHR, 2.1; 95% CI, 1.2 to 3.64; P=0.009) was associated with higher likelihood of DCGF. Notably, both pretransplant coronary artery disease (CAD) and higher BMI were associated with increased risk of death (CAD, aHR, 2.5; 95% CI, 1.69 to 3.71; P<0.001; per 1 kg/m2 higher BMI, aHR, 1.07; 95% CI, 1.04 to 1.11; P<0.001), DCGF, and acute rejection. Nephrectomy at time of transplant and polycystic liver disease were not associated with DCGF/death. Incidence of post-transplant diabetes mellitus was similar between PKD and non-PKD cohorts. Conclusions Recipients with PKD have better long-term graft and patient survival than those with non-PKD. Standard practices of CNI use and promoting HLA match are beneficial in PKD and should continue to be promoted. Further prospective studies investigating the potential benefits of CNI use and medical/surgical interventions to address CAD and the immunologic challenges of obesity are needed. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2021_02_25_KID0001182019.mp3.
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Affiliation(s)
- Gauri Bhutani
- Division of Nephrology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Brad C. Astor
- Division of Nephrology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin,Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Didier A. Mandelbrot
- Division of Nephrology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Lori Mankowski-Gettle
- Department of Radiology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Timothy Ziemlewicz
- Department of Radiology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Shane A. Wells
- Department of Radiology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Leah Frater-Rubsam
- Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin
| | - Vanessa Horner
- Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin,Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin
| | - Courtney Boyer
- Division of Nephrology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Jennifer Laffin
- Department of Pediatrics, University of Wisconsin, Madison, Wisconsin
| | - Arjang Djamali
- Division of Nephrology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin,Division of Transplant Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
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21
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Usui J, Kai H, Kaneko S, Takahashi-Kobayashi M, Hagiwara M, Takahashi K, Oda T, Yamagata K. Kidney transplant patient with immunoglobulin A nephropathy subsequently diagnosed as concurrent autosomal dominant polycystic kidney disease during 17-year follow-up. CEN Case Rep 2020; 9:106-108. [PMID: 31792758 PMCID: PMC7148390 DOI: 10.1007/s13730-019-00436-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 11/18/2019] [Indexed: 11/27/2022] Open
Abstract
A 14-year-old Japanese boy was diagnosed with immunoglobulin A nephropathy resulting in end-stage kidney disease (ESKD). He underwent ABO-compatible living kidney transplantation from his father at the age of 27. In the process of selecting a donor before the transplantation, it turned out that his mother had polycystic kidneys and that her family had a history of hypertension and cerebrovascular diseases. The patient himself also had bilateral multiple kidney cysts, with a normal-sized kidney, confusing us to make the diagnosis of acquired cystic kidney disease (ACKD) or ADPKD difficult at that point. Seventeen years later, his native kidneys showed bilateral swelling with multiple cysts. This, along with the histories of his mother and her relatives and with the existence of multiple liver cysts, led us to confirm the diagnosis of autosomal dominant polycystic kidney disease, not of ACKD. Contrary to previous studies that have suggested the size of cysts both in ADPKD and ACKD reduced with time, the present case showed an increase of 3.0% per year in total kidney volume (TKV) by computed tomography. It suggested the possibility that TKV, after decreasing in the relatively early stage after transplantation, may later increase in the long term after ESKD due to another kidney injury.
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MESH Headings
- Adolescent
- Adult
- Follow-Up Studies
- Glomerulonephritis, IGA/complications
- Glomerulonephritis, IGA/diagnosis
- Humans
- Kidney/diagnostic imaging
- Kidney/pathology
- Kidney Diseases, Cystic/pathology
- Kidney Failure, Chronic/etiology
- Kidney Failure, Chronic/surgery
- Kidney Transplantation/methods
- Male
- Polycystic Kidney, Autosomal Dominant/complications
- Polycystic Kidney, Autosomal Dominant/diagnosis
- Polycystic Kidney, Autosomal Dominant/genetics
- Polycystic Kidney, Autosomal Dominant/pathology
- Proteinuria/diagnosis
- Proteinuria/etiology
- Tomography, X-Ray Computed/methods
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Affiliation(s)
- Joichi Usui
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Hirayasu Kai
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Shuzo Kaneko
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | | | - Masahiro Hagiwara
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Internal Medicine, Saku General Hospital, Saku, Nagano, Japan
| | - Kazuhiro Takahashi
- Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation, Department of Surgery, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Tatsuya Oda
- Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation, Department of Surgery, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Kunihiro Yamagata
- Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
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22
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李 琼, 李 江, 杨 帆, 刘 燕, 邓 文, 刘 如, 胡 杨, 夏 仁, 徐 健, 苗 芸. [Application of immunosuppressants in patients with autosomal dominant polycystic kidney disease after kidney transplantation]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2020; 40:538-543. [PMID: 32895143 PMCID: PMC7225103 DOI: 10.12122/j.issn.1673-4254.2020.04.14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the optimal dose range of immunosuppressants in patients with autosomal dominant polycystic kidney disease (ADPKD) after renal transplantation. METHODS A cohort of 68 patients with ADPKD who received their first renal transplantation between March, 2000 and January, 2018 in our institute were retrospectively analyzed, with 68 non-ADPKD renal transplant recipients matched for gender, age and date of transplant as the control group. We analyzed the differences in patient and renal survival rates, postoperative complications and concentrations of immunosuppressive agents between the two groups at different time points within 1 year after kidney transplantation. The concentrations of the immunosuppressants were also compared between the ADPKD patients with urinary tract infections (UTI) and those without UTI after the transplantation. RESULTS The recipients with ADPKD and the control recipients showed no significantly difference in the overall 1-, 5-, and 10- year patient survival rates (96.6% vs 96.0%, 94.1% vs 93.9%, and 90.6% vs 93.9%, respectively; P > 0.05), 1-, 5-, and 10-year graft survival rates (95.2% vs 96.0%, 90.8% vs 87.2%, and 79.0% vs 82.3%, respectively; P > 0.05), or the incidences of other post- transplant complications including acute rejection, gastrointestinal symptoms, cardiovascular events, pneumonia, and neoplasms (P > 0.05). The plasma concentrations of both tacrolimus and mycophenolate mofetil (MPA) in ADPKD group were significantly lower than those in the control group at 9 months after operation (P < 0.05). The incidence of UTI was significantly higher in ADPKD patients than in the control group (P < 0.05). In patients with ADPKD, those with UTI after transplantation had a significantly higher MPA plasma concentration (P < 0.05). CONCLUSIONS In patients with ADPKD after renal transplant, a higher dose of MPA is associated with a increased risk of UTI, and their plasma concentrations of immunosuppressants for long-term maintenance of immunosuppression regimen can be lower than those in other kidney transplantation recipients.
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Affiliation(s)
- 琼 李
- 南方医科大学第一临床医学院，广东 广州 510515First College of Clinical Medicine Southern Medical University, Guangzhou 510515, China
| | - 江涛 李
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 帆 杨
- 南方医科大学第一临床医学院，广东 广州 510515First College of Clinical Medicine Southern Medical University, Guangzhou 510515, China
| | - 燕娜 刘
- 南方医科大学第一临床医学院，广东 广州 510515First College of Clinical Medicine Southern Medical University, Guangzhou 510515, China
| | - 文锋 邓
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 如敏 刘
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 杨澄 胡
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 仁飞 夏
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 健 徐
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 芸 苗
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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23
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Autosomal Dominant Polycystic Kidney Disease Is a Risk Factor for Posttransplantation Diabetes Mellitus: An Updated Systematic Review and Meta-analysis. Transplant Direct 2020; 6:e553. [PMID: 32548247 PMCID: PMC7213605 DOI: 10.1097/txd.0000000000000989] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 01/29/2020] [Indexed: 12/12/2022] Open
Abstract
Supplemental Digital Content is available in the text. Autosomal dominant polycystic kidney disease (ADPKD) is linked with risk for posttransplantation diabetes mellitus (PTDM), but this association has methodologic limitations like diagnostic criteria. The aim of this study was to use contemporary diagnostic criteria for PTDM and explore any risk association for kidney transplant recipients with ADPKD.
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24
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Banach-Ambroziak E, Jankowska M, Grzywińska M, Szurowska E, Dębska-Ślizień A. Application of Total Kidney Volume and Its Predictive Value in Assessment of Kidney Transplant Waitlist Candidates With Autosomal Dominant Polycystic Kidney Disease. Transplant Proc 2020; 52:2273-2277. [PMID: 32312534 DOI: 10.1016/j.transproceed.2020.02.080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 02/15/2020] [Accepted: 02/22/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent causes of kidney transplantation (KTx) worldwide. About 40% of ADPKD patients require peritransplant native kidney nephrectomy (NKN). The decision regarding qualification for NKN usually relies on the surgeon's expertise. Currently used qualification criteria are subjective and incomparable between clinical centers. There is a need to identify the indications for NKN by applying radiologically based methods to the decision-making process. AIM To assess the usefulness of radiologic parameters in the qualification process of ADPKD waitlist candidates for the NKN procedure. METHOD A retrospective, observational study in a cohort of ADPKD patients in a single institution was conducted. The study included the participation of waitlist candidates and kidney transplant recipients with computed tomography (CT) or magnetic resonance imaging (MRI) obtained in the peritransplant period. The correlation of imaging-based measurements with the results of clinical qualification for the NKN procedure was assessed. RESULTS In the years 2012 to 2019, 19 patients completed the inclusion criteria. Total kidney volume (TKV) values were statistically more significant in the NKN group (n = 10) than in the non-NKN group (n = 9), with medians of 3351 mL and 1654 mL, respectively (P = .016). There were no significant differences between the groups in terms of the ratio of complex cyst volume to TKV, with the NKN group having a ratio of 19.2% and the non-NKN group 15.6% (P = .095). Venous compression was found only in the NKN group (n = 2). CONCLUSIONS TKV highly correlates with the results of clinical qualification for NKN. Radiologic assessment enables the detection of complicated cysts or clinically silent states of venous compression. Pretransplant imaging should be routinely obtained.
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Affiliation(s)
| | - Magdalena Jankowska
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | | | - Edyta Szurowska
- Second Department of Radiology, Medical University of Gdańsk, Gdańsk, Poland
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
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25
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Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, Kumar D, Oberbauer R, Pascual J, Pilmore HL, Rodrigue JR, Segev DL, Sheerin NS, Tinckam KJ, Wong G, Knoll GA. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation 2020; 104:S11-S103. [PMID: 32301874 DOI: 10.1097/tp.0000000000003136] [Citation(s) in RCA: 345] [Impact Index Per Article: 69.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, and immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence, and the strengths of recommendations are provided. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.
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Affiliation(s)
- Steven J Chadban
- Royal Prince Alfred Hospital and Charles Perkins Centre, University of Sydney, Sydney, Australia
| | - Curie Ahn
- Seoul National University, Seoul, South Korea
| | | | - Bethany J Foster
- The Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada
| | | | - Vijah Kher
- Medanta Kidney and Urology Institute, Haryana, India
| | - Deepali Kumar
- University Health Network, University of Toronto, Toronto, Canada
| | | | | | | | | | - Dorry L Segev
- Johns Hopkins University School of Medicine, Baltimore, MD
| | | | | | | | - Gregory A Knoll
- The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, Canada
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26
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He J, Zhou H, Meng J, Zhang S, Li X, Wang S, Shao G, Jin W, Geng X, Zhu S, Yang B. Cardamonin retards progression of autosomal dominant polycystic kidney disease via inhibiting renal cyst growth and interstitial fibrosis. Pharmacol Res 2020; 155:104751. [PMID: 32151678 DOI: 10.1016/j.phrs.2020.104751] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/03/2020] [Accepted: 03/05/2020] [Indexed: 01/12/2023]
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic inherited kidney disease characterized by renal progressive fluid-filled cysts and interstitial fibrosis. Inhibiting renal cyst development and interstitial fibrosis has been proven effective in delaying the progression of ADPKD. The purpose of this study was to discover effective drugs from natural products for preventing and treating ADPKD. Candidate compounds were screened from a natural product library by virtual screening. The Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model, and orthologous mouse model of ADPKD were utilized to determine the pharmacological activities of the candidate compounds. Western blot and morphological analysis were used to investigate underlying mechanisms. The experimental results showed that 0.625, 2.5, and 10 μM cardamonin dose-dependently reduced formation and enlargement in MDCK cyst model. Cardamonin also significantly attenuated renal cyst enlargement in ex vivo mouse embryonic kidneys and PKD mouse kidneys. We found that cardamonin inhibited renal cyst development and interstitial fibrosis by downregulating the MAPK, Wnt, mTOR, and transforming growth factor-β/Smad2/3 signaling pathways. Cardamonin significantly inhibits renal cyst development and interstitial fibrosis, suggesting that cardamonin shows promise as a potential therapeutic drug for preventing and treating ADPKD.
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Affiliation(s)
- Jinzhao He
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Hong Zhou
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China
| | - Jia Meng
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Shun Zhang
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Xiaowei Li
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Shuyuan Wang
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Guangying Shao
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - William Jin
- Division of Graduate Medical Sciences, Boston University School of Medicine, Boston, MA 02118, USA
| | - Xiaoqiang Geng
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Shuai Zhu
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Baoxue Yang
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.
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27
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Foresto RD, Uenishi LT, Pestana RC, Neves RFDCA, Aguiar WF, Tedesco Silva H, Pestana JM. Budd-Chiari Syndrome after Bilateral Nephrectomy for Polycystic Kidney Disease in a Kidney Transplant Recipient. Urol Int 2020; 104:330-332. [PMID: 31896110 DOI: 10.1159/000504514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 10/28/2019] [Indexed: 11/19/2022]
Abstract
We report a rare case of Budd-Chiari syndrome (BCS) as a postoperative complication after bilateral nephrectomy in a kidney transplant recipient with polycystic liver and kidneys. Contrast-enhanced computed tomography of the abdomen showed a narrowed inferior vena cava, compressed by the polycystic liver that moved downwards after nephrectomy. A stenting angioplasty was performed, resulting in remarkable clinical improvement. This case highlights the need for careful evaluation of polycystic kidneys and their anatomic relationship with the liver before nephrectomy, as well as for considering BCS as a differential diagnosis in similar cases.
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Affiliation(s)
- Renato Demarchi Foresto
- Division of Nephrology, Hospital do Rim, Federal University of São Paulo, São Paulo, Brazil,
| | | | | | | | - Wilson Ferreira Aguiar
- Division of Urology, Hospital do Rim, Federal University of São Paulo, São Paulo, Brazil
| | - Hélio Tedesco Silva
- Division of Nephrology, Hospital do Rim, Federal University of São Paulo, São Paulo, Brazil
| | - José Medina Pestana
- Division of Nephrology, Hospital do Rim, Federal University of São Paulo, São Paulo, Brazil
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28
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Anselmo A, Iaria G, Pellicciaro M, Sforza D, Parente A, Campisi A, Cacciatore C, Calafiore E, Pisani G, Tisone G. Native Nephrectomy in Patients With Autosomal Dominant Polycystic Kidney Disease Evaluated for Kidney Transplantation. Transplant Proc 2019; 51:2914-2916. [PMID: 31711576 DOI: 10.1016/j.transproceed.2019.08.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 08/02/2019] [Accepted: 08/27/2019] [Indexed: 11/30/2022]
Abstract
Native nephrectomy (NN) in patients with autosomal dominant polycystic kidney disease (ADPKD) is indicated in cases of recurrent urinary tract infections and hematuria, neoplastic degeneration, and encumbrance. Timing, indication, and surgical approach of NN depends on the symptoms or policy of the center. The aim of our study is to evaluate our experience. In our retrospective study, we included 130 patients with a diagnosis of ADPKD from 530 patients evaluated for renal transplantation from 2011 to 2017. We analyzed the etiologic indication, the timing, and the complications of NN. In our cohort, 53 patients underwent open NN, 85% pre-kidney transplantation (KT), 13% post-KT, and only 1 case simultaneous with KT. In the pre-KT group, indications included: major indication was encumbrance in the. In the post-KT group, the major indication was infection followed by encumbrance, which developed after KT. Complications were: 3 cases of bleeding (1 required relaparotomy, 2 evolved into hematoma and radiological derange); 1 iatrogenic iliac artery injury, which was contextually repaired, and 5 cases of incisional hernia. At 35 ± 7.2 months follow-up, patients' survival was 96%; 1 patient died at the induction of anesthesia and 1 patient from sepsis after double NN and removal of nonfunctional transplanted kidney. NN is not without complications and should be performed when clearly indicated. In our experience, we preferred to perform NN before KT.
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Affiliation(s)
- Alessandro Anselmo
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Giuseppe Iaria
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Marco Pellicciaro
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy.
| | - Daniele Sforza
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Alessandro Parente
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Andrea Campisi
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Chiara Cacciatore
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Eleonora Calafiore
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Gennaro Pisani
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
| | - Giuseppe Tisone
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy
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29
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Lin CH, Chao CT, Wu MY, Lo WC, Lin TC, Wu MS. Use of mammalian target of rapamycin inhibitors in patient with autosomal dominant polycystic kidney disease: an updated meta-analysis. Int Urol Nephrol 2019; 51:2015-2025. [PMID: 31578673 DOI: 10.1007/s11255-019-02292-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/17/2019] [Indexed: 12/19/2022]
Abstract
PURPOSE Mammalian target of rapamycin (mTOR) inhibitors were previously considered a potential therapy for autosomal dominant polycystic kidney disease (ADPKD), but prior studies remained controversial about their efficacy. We performed an updated meta-analysis regarding the therapeutic and adverse effects of mTOR inhibitors in patients with ADPKD. METHODS We systematically searched Cochrane Library, PubMed, EMBASE, and Medline for randomized controlled trials (RCTs) comparing mTOR inhibitors to placebo in ADPKD patients up to August 2019. We calculated weighted mean differences (WMDs) for total kidney volume (TKV), estimated glomerular filtration rates (eGFRs), and weighted odds ratios (ORs) for treatment-related complications between the treatment and the placebo groups, using the random effects model. RESULTS We retrieved a total of 9 RCTs enrolling 784 ADPKD patients receiving rapamycin, sirolimus, or everolimus between 2009 and 2016. The WMDs of TKV and eGFR from baseline to the last measurement were - 31.54 mL (95% confidence interval [CI] - 76.79 to 13.71 mL) and 2.81 mL/min/1.73 m2 (95% CI - 1.85 to 7.46 mL/min/1.73 m2), respectively. Patients receiving mTOR inhibitors had a significantly increased risk of any adverse effects (OR 5.92, 95% CI 3.53-9.94), with the most common ones being aphthous stomatitis (OR 15.45, 95% CI 9.68-24.66) and peripheral edema (OR 3.49, 95% CI 1.31-9.27) compared to placebo users. CONCLUSIONS mTOR inhibitors did not significantly influence renal progression in patients with ADPKD, but were associated with a higher risk of complications. Whether mTOR inhibitors can be an add-on option or second-line agents remain undetermined.
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Affiliation(s)
- Chun-Hung Lin
- Department of Orthopedics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Chia-Ter Chao
- Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, National Taiwan University College of Medicine, Taipei, Taiwan. .,Graduate Institute of Toxicology, National Taiwan University College of Medicine, No. 1, Section 1 Jen-Ai Rd., Taipei, 10051, Taiwan.
| | - Mei-Yi Wu
- Department of Nephrology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.,Department of Primary Care Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Wei-Cheng Lo
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Tsu-Chen Lin
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Mai-Szu Wu
- Department of Nephrology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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30
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Harris T, Sandford R. European ADPKD Forum multidisciplinary position statement on autosomal dominant polycystic kidney disease care: European ADPKD Forum and Multispecialist Roundtable participants. Nephrol Dial Transplant 2019; 33:563-573. [PMID: 29309655 PMCID: PMC6018982 DOI: 10.1093/ndt/gfx327] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Indexed: 02/02/2023] Open
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a chronic, progressive condition characterized by the development and growth of cysts in the kidneys and other organs and by additional systemic manifestations. Individuals with ADPKD should have access to lifelong, multidisciplinary, specialist and patient-centred care involving: (i) a holistic and comprehensive assessment of the manifestations, complications, prognosis and impact of the disease (in physical, psychological and social terms) on the patient and their family; (ii) access to treatment to relieve symptoms, manage complications, preserve kidney function, lower the risk of cardiovascular disease and maintain quality of life; and (iii) information and support to help patients and their families act as fully informed and active partners in care, i.e. to maintain self-management approaches, deal with the impact of the condition and participate in decision-making regarding healthcare policies, services and research. Building on discussions at an international roundtable of specialists and patient advocates involved in ADPKD care, this article sets out (i) the principles for a patient-centred, holistic approach to the organization and delivery of ADPKD care in practice, with a focus on multispecialist collaboration and shared-decision making, and (ii) the rationale and knowledge base for a route map for ADPKD care intended to help patients navigate the services available to them and to help stakeholders and decision-makers take practical steps to ensure that all patients with ADPKD can access the comprehensive multispecialist care to which they are entitled. Further multispecialty collaboration is encouraged to design and implement these services, and to work with patient organizations to promote awareness building, education and research.
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Affiliation(s)
| | | | - Richard Sandford
- Academic Department of Medical Genetics, University of Cambridge School of Clinical Medicine, Cambridge, UK
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Rastogi A, Ameen KM, Al-Baghdadi M, Shaffer K, Nobakht N, Kamgar M, Lerma EV. Autosomal dominant polycystic kidney disease: updated perspectives. Ther Clin Risk Manag 2019; 15:1041-1052. [PMID: 31692482 PMCID: PMC6716585 DOI: 10.2147/tcrm.s196244] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 08/01/2019] [Indexed: 12/17/2022] Open
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and increased kidney volume that eventually leads to end-stage renal disease. ADPKD is considered the fourth leading cause of end-stage renal disease in the United States and globally. Care of patients with ADPKD was, for a long time, limited to supportive lifestyle measures, due to the lack of therapeutic strategies targeting the main pathways involved in the pathophysiology of ADPKD. As the first FDA approved treatment of ADPKD, Vasopressin (V2) receptor blocking agent, tolvaptan, is an urgently awaited advance for ADPKD patients. In our review, we also shed some lights on what is beyond Tolvaptan as there are other medications in the pipeline and many medications have been or are currently being studied in clinical trials such as Tesevatinib, Metformin and Pravastatin, with the goal of slowing the rate of progression of ADPKD by reducing the increase in total kidney volume or maintaining eGFR. Here, we review updates in the perspectives and management of ADPKD.
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Affiliation(s)
- Anjay Rastogi
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Khalid Mohammed Ameen
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Maha Al-Baghdadi
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Kelly Shaffer
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Niloofar Nobakht
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Mohammad Kamgar
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Edgar V Lerma
- Department of Medicine, Divison of Nephrology, University of Illinois at Chicago/Advocate Christ Medical Center, Section of Nephrology, Oak Lawn, IL, USA
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Bellini MI, Charalmpidis S, Brookes P, Hill P, Dor FJMF, Papalois V. Bilateral Nephrectomy for Adult Polycystic Kidney Disease Does Not Affect the Graft Function of Transplant Patients and Does Not Result in Sensitisation. BIOMED RESEARCH INTERNATIONAL 2019; 2019:7423158. [PMID: 31309115 PMCID: PMC6594324 DOI: 10.1155/2019/7423158] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Accepted: 05/19/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Native nephrectomy in Adult Polycystic Kidney Disease (ADPKD) patients is a major operation with controversy related to timing and indications. We present our single centre experience in transplanted patients and future candidates for transplantation. METHODS Retrospective analysis from an anonymised database of bilateral nephrectomies for ADPKD patients. Results were reported as median, range, and percentage. Differences between groups were tested using ANOVA and t-test. Surgery was performed between January 2012 and July 2018. RESULTS Thirty-three patients underwent bilateral native nephrectomy for APKD. 18 had a functioning kidney transplant (transplant group, 55%) while 15 patients were on dialysis (dialysis group, 45%) at the time of surgery; 8 patients of the latter group (24% of the whole cohort) were eventually transplanted. 53% were males, with median age of 55 years (27-71). Indications to surgery were the following: space (symptoms related to the size of the native kidneys or need to create space for transplantation) (59%), recurrent cyst infection (36%), haematuria (15%), pain (24%), and weight loss associated with cystic alteration on imaging (3%). In the transplant group, postoperative kidney function was not affected; haemoglobin serum levels significantly dropped in the whole cohort: 121 (82-150) g/L, versus 108 (58-154) g/L (p<0.001), with 14 patients being transfused perioperatively. Elevation of anti-HLA antibodies was noted in one female patient on dialysis, with no change in DSA levels and no rejection after transplant for all 26 transplanted patients. Median postoperative length of hospital stay was 9 days (6-71). One patient died (3%) after six months. Median follow-up for the whole cohort was 282 days (13-1834). Histopathological examination revealed incidental renal neoplasms in five cases (15%): 1 pT1a papillary renal cell carcinoma and 4 papillary adenomas. CONCLUSIONS Native nephrectomy for ADPKD could be safely performed in case of refractory symptoms, suspect of cancer or to create space for transplantation. It does not affect graft function or DSA status of transplanted patients or the prospect of transplantation of those on the waiting list.
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Affiliation(s)
- Maria Irene Bellini
- Renal and Transplant Directorate, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Sotiris Charalmpidis
- Renal and Transplant Directorate, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Paul Brookes
- Department of Pathology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Peter Hill
- Renal and Transplant Directorate, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Frank J. M. F. Dor
- Renal and Transplant Directorate, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
- Department of Surgery and Cancer, Imperial College, London, UK
| | - Vassilios Papalois
- Renal and Transplant Directorate, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
- Department of Surgery and Cancer, Imperial College, London, UK
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Cheungpasitporn W, Thongprayoon C, Ungprasert P, Wijarnpreecha K, Kaewput W, Leeaphorn N, Bathini T, Chebib FT, Kröner PT. Subarachnoid Hemorrhage in Hospitalized Renal Transplant Recipients with Autosomal Dominant Polycystic Kidney Disease: A Nationwide Analysis. J Clin Med 2019; 8:524. [PMID: 30999564 PMCID: PMC6517948 DOI: 10.3390/jcm8040524] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 04/12/2019] [Accepted: 04/15/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND This study aimed to evaluate the hospitalization rates for subarachnoid hemorrhage (SAH) among renal transplant patients with adult polycystic kidney disease (ADPKD) and its outcomes, when compared to non-ADPKD renal transplant patients. METHODS The 2005-2014 National Inpatient Sample databases were used to identify all hospitalized renal transplant patients. The inpatient prevalence of SAH as a discharge diagnosis between ADPKD and non-ADPKD renal transplant patients was compared. Among SAH patients, the in-hospital mortality, use of aneurysm clipping, hospital length of stay, total hospitalization cost and charges between ADPKD and non-ADPKD patients were compared, adjusting for potential confounders. RESULTS The inpatient prevalence of SAH in ADPKD was 3.8/1000 admissions, compared to 0.9/1000 admissions in non-ADPKD patients (p < 0.01). Of 833 renal transplant patients with a diagnosis of SAH, 30 had ADPKD. Five (17%) ADPKD renal patients with SAH died in hospitals compared to 188 (23.4%) non-ADPKD renal patients (p = 0.70). In adjusted analysis, there was no statistically significant difference in mortality, use of aneurysm clipping, hospital length of stay, or total hospitalization costs and charges between ADPKD and non-ADPKD patients with SAH. CONCLUSION Renal transplant patients with ADPKD had a 4-fold higher inpatient prevalence of SAH than those without ADPKD. Further studies are needed to compare the incidence of overall admissions in ADPKD and non-ADPKD patients. When renal transplant patients developed SAH, inpatient mortality rates were high regardless of ADPKD status. The outcomes, as well as resource utilization, were comparable between the two groups.
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Affiliation(s)
- Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
| | - Karn Wijarnpreecha
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL 32224, USA.
| | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand.
| | - Napat Leeaphorn
- Department of Nephrology, Department of Medicine, Saint Luke's Health System, Kansas City, MO 64111, USA.
| | - Tarun Bathini
- Department of Internal Medicine, University of Arizona, Tucson, AZ 85721, USA.
| | - Fouad T Chebib
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
| | - Paul T Kröner
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL 32224, USA.
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Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet 2019; 393:919-935. [PMID: 30819518 DOI: 10.1016/s0140-6736(18)32782-x] [Citation(s) in RCA: 378] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 10/24/2018] [Accepted: 10/24/2018] [Indexed: 12/15/2022]
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage kidney disease. Multiple clinical manifestations, such as enlarged kidneys filled with growing cysts, hypertension, and multiple extrarenal complications, including liver cysts, intracranial aneurysms, and cardiac valvular disease, show that ADPKD is a systemic disorder. New information derived from clinical research using molecular genetics and advanced imaging techniques has provided enhanced tools for assessing the diagnosis and prognosis for individual patients and their families. Phase 3 randomised, placebo-controlled clinical trials have clarified aspects of disease management and a disease-modifying therapeutic drug is now available for patients with high risk of rapid disease progression. These developments provide a strong basis on which to make clear recommendations about the management of affected patients and families. Implementation of these advances has the potential to delay kidney failure, reduce the symptom burden, lessen the risk of cardiovascular complications, and prolong life.
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Affiliation(s)
- Emilie Cornec-Le Gall
- Service de Néphrologie, Hémodialyse et Transplantation Rénale, Centre Hospitalier Universitaire, Brest, France; UMR1078 Génétique, Génomique Fonctionnelle et Biotechnologies, INSERM, Université de Brest, Brest, France; Université de Bretagne Occidentale, Brest, France
| | - Ahsan Alam
- Division of Nephrology, McGill University Health Centre, Montreal, QC, Canada
| | - Ronald D Perrone
- Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA, USA.
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Change in kidney volume after kidney transplantation in patients with autosomal polycystic kidney disease. PLoS One 2018; 13:e0209332. [PMID: 30589879 PMCID: PMC6307782 DOI: 10.1371/journal.pone.0209332] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 12/04/2018] [Indexed: 12/16/2022] Open
Abstract
Background The indication to bilateral nephrectomy in patients with autosomal dominant polycystic kidney scheduled for kidney transplantation is controversial. Indeed, the progressive enlargement of cysts may increase the risk of complications and the need for nephrectomy. However, very few studies investigated the change in kidney volume after kidney transplantation. Material and methods In this prospective cohort study, the change in native kidney volume in polycystic patients was evaluated with magnetic resonance imaging. Forty patients were included in the study. Kidney diameters and total kidney volume were evaluated with magnetic resonance imaging in patients who underwent simultaneous nephrectomy and kidney transplantation and in patients with kidney transplant alone, before transplantation and 1 year after transplantation. Results There was a significant reduction of kidney volume after transplantation, with a mean degree of kidney diameters reduction varying from 12.24% to 14.43%. Mean total kidney volume of the 55 kidney considered in the analysis significantly reduced from 1617.94 ± 833.42 ml to 1381.42 ± 1005.73 ml (P<0.05), with a mean rate of 16.44% of volume decrease. More than 80% of patients had a volume reduction in both groups. Conclusions Polycystic kidneys volume significantly reduces after kidney transplantation, and this would reduce the need for prophylactic bilateral nephrectomy in asymptomatic patients.
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Effect of Sirolimus on Native Total Kidney Volume After Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Pilot Study. Transplant Proc 2018; 50:1243-1248. [PMID: 29880342 DOI: 10.1016/j.transproceed.2018.02.060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 02/06/2018] [Accepted: 02/19/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND The mammalian target of rapamycin (mTOR) pathway has been shown to be central to cyst formation and growth in patients with autosomal dominant polycystic kidney disease (ADPKD). Drugs that suppress mTOR signaling are frequently used as antiproliferative agents for maintenance immunosuppression in patients who have undergone kidney transplantation. The aim of this study was to determine the effect of sirolimus, an mTOR inhibitor, on cyst volume regression in patients with ADPKD who have undergone renal transplantation. METHODS In this single-center, prospective, open-label, parallel-group, randomized trial, 23 adult patients with ADPKD who successfully underwent renal transplantation from 2008 to 2012 were subsequently randomized (on a 1:1 basis) to a maintenance immunosuppression regimen with either sirolimus (sirolimus, tacrolimus, prednisone) or mycophenolate (mycophenolate, tacrolimus, prednisone). Total kidney volumes were measured by means of high-resolution magnetic resonance imaging within 2 weeks after transplantation and at 1 year. The primary end point was change in total kidney volume at 1 year. RESULTS Sixteen patients completed the 1-year study (8 patients in each group). There was a decrease in kidney volume in both the sirolimus group (percentage change from baseline, 20.5%; P < .001) and mycophenolate group (percentage change from baseline, 17%; P = .048), but there was no significant difference in percentage change of total kidney volume between the groups (P = .665). CONCLUSIONS In ADPKD patients at 1 year after kidney transplantation, there was a similar decrease in polycystic kidney volume in patients receiving an immunosuppression regimen containing sirolimus compared with patients receiving mycophenolate.
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Jankowska M, Kuźmiuk-Glembin I, Skonieczny P, Dębska-Ślizień A. Native Nephrectomy in Renal Transplant Recipients With Autosomal Dominant Polycystic Kidney Disease. Transplant Proc 2018; 50:1863-1867. [DOI: 10.1016/j.transproceed.2018.02.100] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Accepted: 02/06/2018] [Indexed: 12/26/2022]
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Kocyigit I, Eroglu E, Gungor O. Clinical problems in hemodialysis patients with autosomal dominant polycystic kidney disease. Semin Dial 2018; 31:268-277. [DOI: 10.1111/sdi.12696] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Ismail Kocyigit
- Department of Nephrology; Erciyes University Medical Faculty; Kayseri Turkey
| | - Eray Eroglu
- Department of Nephrology; Erciyes University Medical Faculty; Kayseri Turkey
| | - Ozkan Gungor
- Department of Nephrology; Sutcu Imam University Medical Faculty; Kahramanmaras Turkey
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Montaña A, Patiño N, Larrate C, Zambrano FA, Martínez J, Lozano H, Lozano E. Actualización en enfermedad renal poliquística. REVISTA DE LA FACULTAD DE MEDICINA 2018. [DOI: 10.15446/revfacmed.v66n1.60760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Introducción. La enfermedad renal poliquística (PKD, por su sigla en inglés) es una enfermedad genética frecuente en la que se desarrollan de forma progresiva lesiones quísticas que reemplazan el parénquima renal. Es una causa de insuficiencia renal terminal y una indicación común para diálisis y trasplante renal. Existen dos presentaciones de esta enfermedad que se distinguen por sus patrones de herencia: la enfermedad renal poliquística dominante (ADPKD, por su sigla en inglés) y la enfermedad renal poliquística recesiva (ARPKD, por su sigla en inglés).Objetivo. Resumir los aspectos más relevantes de la enfermedad renal: epidemiología, fisiopatología, diagnóstico, manifestaciones clínicas, tratamiento y pronóstico.Materiales y métodos. Revisión sistemática de la literatura en las bases de datos PubMed, Lilacs, UptoDate y Medline con los siguientes términos: enfermedades renales poliquísticas, riñón poliquístico autosómico dominante y riñón poliquístico autosómico recesivo.Resultados. Se encontraron 271 artículos y se escogieron 64 con base en su importancia.Conclusiones. Todo paciente con enfermedad renal poliquística en insuficiencia renal grado V debe ser estudiado para un trasplante renal; en la gran mayoría de los casos no se encontrará contraindicación para realizarlo.
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Jean RA, Alexandre M, Yoo PS. Kidney Transplantation With and Without Native Nephrectomy for Polycystic Kidney Disease: Results of the National Inpatient Sample and the Rationale for a 2-Staged Procedure. J Am Coll Surg 2017; 226:1079-1084. [PMID: 29224797 DOI: 10.1016/j.jamcollsurg.2017.11.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 11/20/2017] [Accepted: 11/20/2017] [Indexed: 11/28/2022]
Abstract
BACKGROUND Polycystic kidney disease (PKD) is one of the most common causes of end-stage renal disease requiring hemodialysis or transplantation. In patients requiring transplantation, there are several indications for native nephrectomy, including recurrent cyst infection, bleeding, or to provide room for the graft. There is disagreement about whether it is advisable to perform kidney transplantation alone (KT), or to perform KT with simultaneous native nephrectomy (KTN). We compared postoperative outcomes of KTN and KT in a large national cohort. STUDY DESIGN The Nationwide Inpatient Sample (NIS) between 2000 and 2014 was examined for a diagnosis of PKD with evidence for KT or KTN. Logistic regression, adjusting for age, sex, comorbidity, and hospital region, was used to compare groups for the need for blood transfusion, need for critical care interventions, and development of postoperative complications. RESULTS A total of 4,003 hospitalizations were identified, which was representative of 19,302 weighted discharges nationally. In adjusted logistic regression models, KTN demonstrated significantly higher risk for blood transfusion (odds ratio [OR] 2.06; 95% CI 1.44 to 2.96; p < 0.0001), postoperative complications (OR 1.44; 95% CI 1.05 to 1.96; p = 0.02), and critical care interventions (OR 1.44; 95% CI 1.07 to 1.95; p = 0.02). Other significant predictors for blood transfusion included female sex (OR 1.76; 95% CI 1.45 to 2.13; p < 0.0001), age older than 61 years (OR 1.60; 95% CI 1.21 to 2.10; p = 0.001), and Charlson comorbidity score ≥2 (OR 1.52; 95% CI 1.10 to 2.09; p = 0.01). CONCLUSIONS Among patients with PKD, in comparison with KTN, KT alone represents a decreased risk for negative postoperative outcomes. A 2-staged procedure should be considered, when feasible, to minimize adverse patient outcomes.
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Affiliation(s)
- Raymond A Jean
- Department of Surgery, Yale School of Medicine, New Haven, CT; National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | | | - Peter S Yoo
- Section of Transplantation and Immunology, Department of Surgery, Yale School of Medicine, New Haven, CT.
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Barbouch S, Hajji M, Hedri H, El Younsi F, Ben Hamida F, Bacha MM, Ounissi M, Abderrahim E, Ben Abdallah T. Outcome of Kidney Transplant in Patients with Polycystic Kidney Disease: A Single-Center Study in Tunisia. EXP CLIN TRANSPLANT 2017; 15:196-199. [PMID: 28260467 DOI: 10.6002/ect.mesot2016.p78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Autosomal dominant polycystic kidney disease is a common cause of end-stage renal disease and a common indication for renal transplant. This study was undertaken to evaluate the demographics, outcomes, and complications of renal transplant in patients with autosomal dominant polycystic kidney disease compared with other nephropathies. MATERIALS AND METHODS In a retrospective case-control design, we reviewed the records of 7 patients with autosomal dominant polycystic kidney disease from a total of 701 renal transplant patients over a 30-year period (1986-2016). For each patient, a matched control was selected based on sex, age, year of transplant, and type of kidney donor. We excluded patients who underwent kidney transplant abroad and those with a follow-up period of less than 2 years. RESULTS The number of patients with autosomal dominant polycystic kidney disease requiring transplant at our center was estimated at 0.23 per year, and the condition represented 1.57% of initial nephropathy causes. The mean patient age at transplant was 50.8 ± 8.05 years. There were 5 male and 2 female patients in the case group, with a male-to-female ratio of 2.5. The source of the graft was predominantly a living related donor (5/7). Four patients had extrarenal manifestations, the most common of which were liver cysts (3 patients). Rejection occurred in a single study patient (14.2%) and in 4 control patients (57.1%; P = .51). Two patients did not develop any complications. Complications noted after transplant included infection (3/7 cases vs 2/7 controls; P= .67) and cerebrovascular accidents (2/7 cases vs 0/7 controls). CONCLUSIONS Further studies with longer follow-up and greater numbers of patients are needed to compare more precisely the complications and results of transplant between patients with autosomal dominant polycystic kidney disease and other kidney transplant recipients.
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Affiliation(s)
- Samia Barbouch
- Department of Nephrology, Charles Nicolle Hospital, Tunis, Tunisia
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Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, Gallon L, Garvey CA, Guleria S, Li PKT, Segev DL, Taler SJ, Tanabe K, Wright L, Zeier MG, Cheung M, Garg AX. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation 2017; 101:S1-S109. [PMID: 28742762 PMCID: PMC5540357 DOI: 10.1097/tp.0000000000001769] [Citation(s) in RCA: 233] [Impact Index Per Article: 29.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 03/20/2017] [Indexed: 12/17/2022]
Abstract
The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1-S109.
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Affiliation(s)
| | | | | | | | - Josefina Alberú
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | | | | | - Dorry L. Segev
- Johns Hopkins University, School of Medicine, Baltimore, MD
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Flahault A, Knebelmann B, Nataf F, Trystram D, Grünfeld JP, Joly D. [Screening and management of intracranial aneurisms in patients with autosomal dominant polycystic kidney disease]. Nephrol Ther 2017; 13 Suppl 1:S147-S153. [PMID: 28577737 DOI: 10.1016/j.nephro.2017.01.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 01/21/2017] [Indexed: 12/17/2022]
Abstract
Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease. Intracranial aneurysm prevalence in this population is four to five times higher than the prevalence in the general population. The most frequent complication of intracranial aneurysms is rupture with subarachnoidal hemorrhage, which is associated with a high morbidity and mortality. The only identified risk factor for unruptured intracranial aneurysm is a family history of intracranial aneurysm. However, most cases of aneurysm rupture occur without any family history of intracranial aneurysm. Magnetic resonance angiography without contrast medium injection facilitates screening, and progress have been made in preventive (endovascular or neurosurgical) treatment of intracranial aneurysm. Recommendations have recently been published concerning intracranial aneurysm screening, and suggest screening patients with autosomal dominant polycystic kidney disease and a family history of intracranial aneurysm, those who have an at-risk activity and those who request screening despite adequate information. Conflicting opinions exist, however, in the literature. Furthermore, a study of practice was conducted among French-speaking nephrologists in Europe and showed that approximately a third of the participants were in favor of systematic screening for intracranial aneurysm in all patients with autosomal dominant polycystic kidney disease. Beyond intracranial aneurysm prevalence, it is necessary to better define rupture rates in the autosomal dominant polycystic kidney disease population, with and without familial history of intracranial aneurysm. This would allow optimizing intracranial aneurysm screening practices in autosomal dominant polycystic kidney disease.
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Affiliation(s)
- Adrien Flahault
- Faculté de médecine, université Paris-Descartes, 149, rue de Sèvres, 75015 Paris, France; Service de néphrologie, hôpital Necker-enfants malades, 149, rue de Sèvres, 75015 Paris, France; Laboratory of Central Neuropeptides in the Regulation of Body Fluid Homeostasis and Cardiovascular Functions, Center of Interdisciplinary Research in Biology (CIRB), collège de France, 11, place Marcelin-Berthelot, 75231 Paris cedex 05, France; Inserm U1050, 11, place Marcelin-Berthelot, 75231 Paris cedex 05, France
| | - Bertrand Knebelmann
- Faculté de médecine, université Paris-Descartes, 149, rue de Sèvres, 75015 Paris, France; Service de néphrologie, hôpital Necker-enfants malades, 149, rue de Sèvres, 75015 Paris, France
| | - François Nataf
- Faculté de médecine, université Paris-Descartes, 149, rue de Sèvres, 75015 Paris, France; Inserm UMR 894, 2, ter rue d'Alésia, 75014 Paris, France; Service de neurochirurgie, centre hospitalier Sainte-Anne, 1, rue Cabanis, 75674 Paris cedex 14, France
| | - Denis Trystram
- Faculté de médecine, université Paris-Descartes, 149, rue de Sèvres, 75015 Paris, France; Inserm UMR 894, 2, ter rue d'Alésia, 75014 Paris, France; Service de neuroradiologie, centre hospitalier Sainte-Anne, 1, rue Cabanis, 75674 Paris cedex 14, France
| | - Jean-Pierre Grünfeld
- Faculté de médecine, université Paris-Descartes, 149, rue de Sèvres, 75015 Paris, France; Service de néphrologie, hôpital Necker-enfants malades, 149, rue de Sèvres, 75015 Paris, France
| | - Dominique Joly
- Faculté de médecine, université Paris-Descartes, 149, rue de Sèvres, 75015 Paris, France; Service de néphrologie, hôpital Necker-enfants malades, 149, rue de Sèvres, 75015 Paris, France.
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Messa P, Alfieri CM, Montanari E, Ferraresso M, Cerutti R. ADPKD: clinical issues before and after renal transplantation. J Nephrol 2016; 29:755-763. [DOI: 10.1007/s40620-016-0349-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 08/29/2016] [Indexed: 12/17/2022]
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Tillou X, Timsit MO, Sallusto F, Culty T, Verhoest G, Doerfler A, Thuret R, Kleinclauss F. [Polycystic kidney disease and kidney transplantation]. Prog Urol 2016; 26:993-1000. [PMID: 27665410 DOI: 10.1016/j.purol.2016.08.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Revised: 08/22/2016] [Accepted: 08/22/2016] [Indexed: 12/28/2022]
Abstract
OBJECTIVES To perform a state of the art about autosomal dominant polykystic kidney disease (ADPKD), management of its urological complications and end stage renal disease treatment modalities. MATERIAL AND METHODS An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): "autosomal dominant polykystic kidney disease", "complications", "native nephrectomy", "kidney transplantation". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 3779 articles. After reading titles and abstracts, 52 were included in the text, based on their relevance. RESULTS ADPKD is the most inherited renal disease, leading to end stage renal disease requiring dialysis or renal transplantation in about 50% of the patients. Many urological complications (gross hematuria, cysts infection, renal pain, lithiasis) of ADPKD required urological management. The pretransplant evaluation will ask the challenging question of native nephrectomy only in case of recurrent kidney complications or large kidney not allowing graft implantation. The optimum timing for native nephrectomy will depend on many factors (dialysis or preemptive transplantation, complication severity, anuria, easy access to transplantation, potential living donor). CONCLUSION Pretransplant management of ADPKD is challenging. A conservative strategy should be promoted to avoid anuria (and its metabolic complications) and to preserve a functioning low urinary tract and quality of life. When native nephrectomy should be performed, surgery remains the gold standard but renal arterial embolization may be a safe option due to its low morbidity.
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Affiliation(s)
- X Tillou
- Service d'urologie et transplantation, CHU Côte de Nacre, 14000 Caen, France
| | - M-O Timsit
- Service d'urologie, hôpital européen Georges-Pompidou, 75015 Paris, France; Université Paris Descartes, 75006 Paris, France
| | - F Sallusto
- Département d'urologie et transplantation, CHU de Toulouse, 31400 Toulouse, France
| | - T Culty
- Service d'urologie, CHU d'Angers, 49100 Angers, France
| | - G Verhoest
- Service d'urologie, CHU de Rennes, 35000 Rennes, France
| | - A Doerfler
- Service d'urologie et transplantation, CHU Côte de Nacre, 14000 Caen, France
| | - R Thuret
- Service d'urologie, CHU Lapeyronie, 34000 Montpellier, France; Université de Montpellier, 34000 Montpellier, France
| | - F Kleinclauss
- Service d'urologie et transplantation, CHRU de Besançon, 3, boulevard A.-Fleming, 25000 Besançon, France; Université de Franche-Comté, 25000 Besançon, France; Inserm UMR 1098, 25000 Besançon, France.
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Simultaneous Native Nephrectomy and Kidney Transplantation in Patients With Autosomal Dominant Polycystic Kidney Disease. PLoS One 2016; 11:e0155481. [PMID: 27257690 PMCID: PMC4892472 DOI: 10.1371/journal.pone.0155481] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 04/29/2016] [Indexed: 12/17/2022] Open
Abstract
Introduction To evaluate the feasibility of simultaneous unilateral nephrectomy with kidney transplantation and to determine the effect of this procedure on perioperative morbidity and mortality and graft and patient survival. Methods Between January 2000 and May 2015, 145 patients with autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplantation. Of those, 40 (27.5%) underwent concurrent ipsilateral native nephrectomy (group NT). Patients in group NT were compared with patients with ADPKD not undergoing concurrent nephrectomy (group NT-) and asymptomatic patients undergoing pretransplant nephrectomy (group PNT). Results The average follow-up was 66 months. The graft survival rate at 1 and 5 years was 95% and 87.5% versus 93% and 76.2% in the NT and NT- groups, respectively (P = .903 and P = .544, respectively); 1-year patient survival was 100% for NT and 97% for NT- patients (P = .288), whereas 5-year patient survival was 100% and 92% for NT and NT- groups, respectively (P = .128). After propensity score matching (34 patients per group) no significant differences were observed in 1-year (97.1% in NT and 94.1%; P = 1) and 5-year (88.2% in NT and 91.2% in NT-; P = 1) graft survival, and in 1-year (100% for both groups; P = 1) and 5-year (100% in NT and 94.1% in NT-; P = 1) patient survival. Perioperative mortality was 0% among NT and 1.2% among NT- patients, whereas perioperative surgical complications were similar in both groups. One- and 5-year graft and patient survival were similar between the NT and PNT groups, but patients in the PNT group had significantly lower levels of hemoglobin and residual diuresis volumes at the time of transplant. Moreover, PNT patients had a longer pretransplant dialysis and a longer time on the waiting list. Conclusions Simultaneous unilateral nephrectomy does not have a negative effect on patient and graft survival in patients with ADPKD and is associated with low morbidity. Pretransplant nephrectomy should be restricted only to highly symptomatic patients, whereas unilateral nephrectomy in asymptomatic patients should be performed during kidney transplantation only if massive kidney size precludes graft positioning.
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Cheungpasitporn W, Thongprayoon C, Vijayvargiya P, Anthanont P, Erickson SB. The Risk for New-Onset Diabetes Mellitus after Kidney Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta-Analysis. Can J Diabetes 2016; 40:521-528. [PMID: 27184299 DOI: 10.1016/j.jcjd.2016.03.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 02/09/2016] [Accepted: 03/01/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVES New-onset diabetes after kidney transplantation (NODAT) is associated with both renal allograft failure and increased rates of mortality. The objective of this meta-analysis was to evaluate the risk for NODAT in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through July 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk for NODAT in patients with ADPKD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS Included in the analysis were 12 cohort studies, which comprised 1379 patients with ADPKD of a total of 9849 patients who had undergone kidney transplants. The pooled RRs of NODAT in patients with ADPKD were 1.92 (95% CI, 1.36 to 2.70). When meta-analysis was limited only to studies with confounder-adjusted analysis, the pooled RRs for NODAT were 1.98 (95% CI, 1.33 to 2.94). However, the association between NODAT requiring insulin treatment was insignificant, with pooled RRs of 1.57 (95% CI, 0.75 to 3.27). CONCLUSIONS Our meta-analysis demonstrates a significant association between ADPKD and NODAT in recipients of kidney transplants. The findings of this study may impact clinical management and follow up for patients with ADPKD after kidney transplantation.
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Affiliation(s)
- Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States.
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
| | - Priya Vijayvargiya
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Pimjai Anthanont
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota, United States; Faculty of Medicine, Thammasat University Hospital, Bangkok, Thailand
| | - Stephen B Erickson
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
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Flahault A, Trystram D, Fouchard M, Knebelmann B, Nataf F, Joly D. Screening for Unruptured Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease: A Survey of 420 Nephrologists. PLoS One 2016; 11:e0153176. [PMID: 27054719 PMCID: PMC4824518 DOI: 10.1371/journal.pone.0153176] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 03/24/2016] [Indexed: 12/18/2022] Open
Abstract
Background Despite a high prevalence of intracranial aneurysm (ICA) in autosomal dominant polycystic kidney disease (ADPKD), rupture events are rare. The current recommendations for ICA screening are based on expert opinions and studies with low levels of evidence. Objectives The aim of our study was to describe the attitudes of practicing nephrologists in Europe towards screening for ICA using magnetic resonance angiography (MRA). Methods We conducted a web-based survey among 1315 European French-speaking nephrologists and nephrology residents. An anonymous, electronic questionnaire including 24 independent questions related to ICA screening modalities, indications and participant profiles was sent by email between September and December 2014. Four hundred and twenty nephrologists (mostly from France) participated, including 31 nephrology residents; the response rate was 32%. Results Systematic screening for ICA was advocated by 28% of the nephrologists. A family history of ICA rupture, sudden death, stroke and migraine were consensual indications for screening (> 90% of the panel). In other clinical situations largely not covered by the recommendations (pregnancy, nephrectomy, kidney transplantation, cardiac or hepatic surgery, uncontrolled hypertension, lack of familial ADPKD history, at-risk activity, tobacco use), the attitudes towards screening were highly divergent. ICA screening was influenced by nephrologists experience with ADPKD and by their practice setting. The majority of participants (57%) would not repeat a normal ICA screening. Only a few participants (22%) knew that non-contrast MRA was the reference diagnostic tool for ICA screening, whereas most participants thought that contrast enhancement was necessary to screen for ICA. The results from the nephrology residents were analyzed separately and yielded similar results. Conclusion This practice survey revealed that most nephrologists follow the current recommendations for the initial screening of ICAs. However, more than a quarter of the panel was in favor of systematic ICA screening, most nephrologists did not know that contrast medium was not necessary to screen for ICA using MRA, and many areas of uncertainty remain.
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Affiliation(s)
- Adrien Flahault
- Université Paris-Descartes; Faculté de Médecine; AP-HP; Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France
| | - Denis Trystram
- Université Paris-Descartes, INSERM UMR 894, Service de Neuroradiologie, Centre Hospitalier Sainte-Anne, Paris, France
| | - Marie Fouchard
- Université Paris-Descartes; Faculté de Médecine; AP-HP; Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France
| | - Bertrand Knebelmann
- Université Paris-Descartes; Faculté de Médecine; AP-HP; Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France
| | - François Nataf
- Université Paris-Descartes, INSERM UMR 894, Service de Neurochirurgie, Centre Hospitalier Sainte-Anne, Paris, France
| | - Dominique Joly
- Université Paris-Descartes; Faculté de Médecine; AP-HP; Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France
- * E-mail:
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Clinical Outcome of Simultaneous Native Nephrectomy and Kidney Transplantation in Patients With Autosomal Dominant Polycystic Kidney Disease. Transplant Proc 2016; 48:840-3. [DOI: 10.1016/j.transproceed.2015.08.047] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Accepted: 08/18/2015] [Indexed: 12/23/2022]
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Venugopal J, Blanco G. Ouabain Enhances ADPKD Cell Apoptosis via the Intrinsic Pathway. Front Physiol 2016; 7:107. [PMID: 27047392 PMCID: PMC4805603 DOI: 10.3389/fphys.2016.00107] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Accepted: 03/07/2016] [Indexed: 11/13/2022] Open
Abstract
Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly influenced by factors circulating in blood. We have shown that the hormone ouabain enhances several characteristics of the ADPKD cystic phenotype, including the rate of cell proliferation, fluid secretion and the capacity of the cells to form cysts. In this work, we found that physiological levels of ouabain (3 nM) also promote programmed cell death of renal epithelial cells obtained from kidney cysts of patients with ADPKD (ADPKD cells). This was determined by Alexa Fluor 488 labeled-Annexin-V staining and TUNEL assay, both biochemical markers of apoptosis. Ouabain-induced apoptosis also takes place when ADPKD cell growth is blocked; suggesting that the effect is not secondary to the stimulatory actions of ouabain on cell proliferation. Ouabain alters the expression of BCL family of proteins, reducing BCL-2 and increasing BAX expression levels, anti- and pro-apoptotic mediators respectively. In addition, ouabain caused the release of cytochrome c from mitochondria. Moreover, ouabain activates caspase-3, a key “executioner” caspase in the cell apoptotic pathway, but did not affect caspase-8. This suggests that ouabain triggers ADPKD cell apoptosis by stimulating the intrinsic, but not the extrinsic pathway of programmed cell death. The apoptotic effects of ouabain are specific for ADPKD cells and do not occur in normal human kidney cells (NHK cells). Taken together with our previous observations, these results show that ouabain causes an imbalance in cell growth/death, to favor growth of the cystic cells. This event, characteristic of ADPKD, further suggests the importance of ouabain as a circulating factor that promotes ADPKD progression.
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Affiliation(s)
- Jessica Venugopal
- Department of Molecular and Integrative Physiology and The Kidney Institute, University of Kansas Medical Center Kansas City, KS, USA
| | - Gustavo Blanco
- Department of Molecular and Integrative Physiology and The Kidney Institute, University of Kansas Medical Center Kansas City, KS, USA
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